Emergence and dissemination of extensively drug-resistant ST307 Klebsiella pneumoniae in China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to global public health. Identifying high-risk clones that facilitate the global dissemination of carbapenemases is essential for developing effective strategies to address this challenge. Here, we collected 29 ST307 CRKP isolates harbouring the bla KPC-2 and/or bla NDM-5 genes from three hospitals. bla NDM-5 was carried by the IncX3 plasmid, and bla KPC-2 was located on an IncFII plasmid. All of them were horizontally transmissible as verified by plasmid conjugation assays. Phylogenetic analysis revealed a clonal outbreak involving 27 of the isolates in this study and further demonstrated an emerging trend of bla KPC-2- and bla NDM-5-positive CRKP strains within the ST307 lineages in China since 2023. Resistance to 'last-resort' antibiotics mediated by genetic mutations is a major contributor to treatment failure in CRKP infections. In this study, we functionally confirmed that the plasmid-borne tet(A)I235F mutation confers resistance to both tigecycline and eravacycline. The results of the murine bloodstream infection model further demonstrated that the tet(A)I235F mutation increased the treatment cost of tigecycline. Furthermore, we found colistin resistance in ST307 CRKP primarily mediated by mutations in the mgrB and pmrB genes. Specific mutation patterns, including mgrB disruption by IS5D, mgrB W20* and pmrB S203P substitutions, were identified in nine colistin-resistant ST307 CRKP isolates in this study. These findings highlight the need for enhanced surveillance and control measures to prevent the potential widespread outbreak of extensively drug-resistant ST307 isolates in China.